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脊髓不完全损伤后脊髓背角深层中间神经元自发恢复的电生理特征

Electrophysiological characterization of spontaneous recovery in deep dorsal horn interneurons after incomplete spinal cord injury.

作者信息

Rank M M, Flynn J R, Galea M P, Callister R, Callister R J

机构信息

School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, 2308 NSW, Australia.

Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, 3050 VIC, Australia.

出版信息

Exp Neurol. 2015 Sep;271:468-78. doi: 10.1016/j.expneurol.2015.07.002. Epub 2015 Jul 12.

Abstract

In the weeks and months following an incomplete spinal cord injury (SCI) significant spontaneous recovery of function occurs in the absence of any applied therapeutic intervention. The anatomical correlates of this spontaneous plasticity are well characterized, however, the functional changes that occur in spinal cord interneurons after injury are poorly understood. Here we use a T10 hemisection model of SCI in adult mice (9-10 wks old) combined with whole-cell patch clamp electrophysiology and a horizontal spinal cord slice preparation to examine changes in intrinsic membrane and synaptic properties of deep dorsal horn (DDH) interneurons. We made these measurements during short-term (4 wks) and long-term (10 wks) spontaneous recovery after SCI. Several important intrinsic membrane properties are altered in the short-term, but recover to values resembling those of uninjured controls in the longer term. AP discharge patterns are reorganized at both short-term and long-term recovery time points. This is matched by reorganization in the expression of voltage-activated potassium and calcium subthreshold-currents that shape AP discharge. Excitatory synaptic inputs onto DDH interneurons are significantly restructured in long-term SCI mice. Plots of sEPSC peak amplitude vs. rise times suggest considerable dendritic expansion or synaptic reorganization occurs especially during long-term recovery from SCI. Connectivity between descending dorsal column pathways and DDH interneurons is reduced in the short-term, but amplified in long-term recovery. Our results suggest considerable plasticity in both intrinsic and synaptic mechanisms occurs spontaneously in DDH interneurons following SCI and takes a minimum of 10 wks after the initial injury to stabilize.

摘要

在不完全性脊髓损伤(SCI)后的数周和数月内,在没有任何应用治疗干预的情况下,功能会出现显著的自发恢复。这种自发可塑性的解剖学相关性已得到很好的表征,然而,损伤后脊髓中间神经元发生的功能变化却知之甚少。在这里,我们使用成年小鼠(9 - 10周龄)的T10半切模型,结合全细胞膜片钳电生理学和水平脊髓切片制备,来研究深背角(DDH)中间神经元的内在膜特性和突触特性的变化。我们在SCI后的短期(4周)和长期(10周)自发恢复期间进行了这些测量。几个重要的内在膜特性在短期内发生改变,但在长期内恢复到类似于未损伤对照的值。动作电位(AP)发放模式在短期和长期恢复时间点均发生重组。这与塑造AP发放的电压激活钾离子和钙离子阈下电流表达的重组相匹配。在长期SCI小鼠中,DDH中间神经元上的兴奋性突触输入发生了显著重组。微小兴奋性突触后电流(sEPSC)峰值幅度与上升时间的关系图表明,特别是在从SCI长期恢复期间,发生了相当大的树突扩展或突触重组。下行背柱通路与DDH中间神经元之间的连接性在短期内降低,但在长期恢复中增强。我们的结果表明,SCI后DDH中间神经元的内在和突触机制均会自发出现相当大的可塑性,并且在初始损伤后至少需要10周才能稳定下来。

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